Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
  • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
  • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
  • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/04—Antibacterial agents
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
  • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
  • Y02P20/00—Technologies relating to chemical industry
  • Y02P20/50—Improvements relating to the production of bulk chemicals
  • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

• the resulting compounds of formula (I) are useful intermediates in the preparation of anti-bacterial compounds, called penems, as described, e.g., in U.K. Patent No. 2,111,496-B.
• Said oxidation is carried out by means of organic peracids, such as e.g., monoperphthalic or m-chloroperbenzoic acid.
• the object of the present invention is therefore to provide a easy and cheap method for oxidizing 4-acylazetidinones (II) to 4-acyloxyazetidinones (I), such method being capable to be applied to substrates with a non-protected alcoholic function.
• Another object is to provide a method free from the corrosion and safely problems, which are generally encountered when organic peracid solutions are employed.
• an organic phase including a 4-acylazetidinone (II) and an onium salt dissolved in a medium immiscible with water, and
• an aqueous solution including an alkali or alkaline-earth metal salt of an organic or inorganic peracid including an alkali or alkaline-earth metal salt of an organic or inorganic peracid.
• Illustrative 4-acylazetidinones (II) which can be oxidized according to the present invention are those wherein R 1 represents a hydrogen atom or a silyl group (e.g., trimethylsilyl, and also ter-butyldimethylsilyl group), R 2 represents a hydrogen atom, a non-substituted or substituted benzyl group (e.g., p-methoxybenzyl) or a non-substituted or substituted phenyl group (e.g., p-methoxyphenyl) and R 3 represents a phenyl or alkyl group (e.g., methyl).
• R 1 represents a hydrogen atom or a silyl group (e.g., trimethylsilyl, and also ter-butyldimethylsilyl group)
• R 2 represents a hydrogen atom, a non-substituted or substituted benzyl group (e.g.,
• the raw materials according to formula (II) are known compounds or can be prepared using methods described in the literature, such as the above-metnioned papers and patents.
• the general formula (I) encompasses all the optical forms (racemic or optically active).
• the preferred configurations are 3S, 4R for azetidinone and R for the carbon atom in the chain carrying the hydroxy group, so that the penem compounds resulting from the compounds of formula (I) have the final, preferred stereochemistry [5R,6S, (1R)].
• M represents a nitrogen or phosphorus atoms
• Y - represents an inorganic stable anion such as Cl - or HSO 4 - and R 4 , R 5 , R 6 and R 7 which can be the same or different, represent hydrocarbyl groups with a total content of carbon atoms between about 10 and 70.
• Illustrative onium salts which can be advantageously employed in the reaction, are dimethyl [dioctadecyl (75%)+ dihexadecyl (25%)] ammonium chloride (marketed as ARQUAD 2HT) and methyltrioctylammonium chloride (marketed as ALIQUAT 336).
• solvent a solvent immiscible with water, such as ethyl acetate or chloroform, can be employed.
• oxidizing agent it can be employed in the reaction any alkali or alkaline-earth metal salt of any organic or inorganic peracid.
• the reaction is carried out by vigorously stirring the two-phase mixture at temperatures between about 5° and 60° C., preferably between 15° and 45° C.
• concentration of 4-acylazetidinone (II) in the organic phase can range between about 2 and 25% by weigh.
• concentration of the peroxy compound in the aqueous phase can range between about 2 and 15% by weight, its amount being in the range between about 1 and 5 moles per mole of 4-acylazetidinone (II).
• the onium salt is employed in amounts ranging between about 0.01 and 0.1 moles per mole of 4-acylazetidinone (II).
• the acidity of the solution can be further controlled by having the peroxy compound dissolved not in water, but in a buffer solution such as, e.g., a sodium phosphate solution at pH near 7.
• a buffer solution such as, e.g., a sodium phosphate solution at pH near 7.
• the duration of the reaction can range between about 5 and 48 hours depending on the selected conditions and, at the end of this period, 4-acyloxyazetidinone (I) is isolated according to conventional techniques.
• the example 1 has been repeated replacing CAROAT.sup.® by 1.98 g of acid magnesium monoperoxyphtalate hexahydrate (H-48; 4 mmoles), employing 20 ml of Na phosphate buffer at pH 6.6 and extending the reaction time to 10 hours.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Communicable Diseases (AREA)
• Pharmacology & Pharmacy (AREA)
• Oncology (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Cephalosporin Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

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Citations (5)

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• 1986
  • 1986-10-15 IT IT22003/86A patent/IT1197873B/it active
• 1987
  • 1987-10-09 CH CH3972/87A patent/CH676983A5/it not_active IP Right Cessation
  • 1987-10-09 GR GR871558A patent/GR871558B/el unknown
  • 1987-10-09 NZ NZ222112A patent/NZ222112A/xx unknown
  • 1987-10-12 AT AT2683/87A patent/AT392965B/de not_active IP Right Cessation
  • 1987-10-12 AU AU79551/87A patent/AU592231B2/en not_active Ceased
  • 1987-10-12 DE DE19873734468 patent/DE3734468A1/de not_active Withdrawn
  • 1987-10-12 FI FI874471A patent/FI88294C/fi not_active IP Right Cessation
  • 1987-10-12 FR FR878714059A patent/FR2605318B1/fr not_active Expired - Fee Related
  • 1987-10-12 DK DK533287A patent/DK167571B1/da not_active IP Right Cessation
  • 1987-10-12 IL IL84149A patent/IL84149A/xx not_active IP Right Cessation
  • 1987-10-13 ES ES8702919A patent/ES2005035A6/es not_active Expired
  • 1987-10-13 ZA ZA877683A patent/ZA877683B/xx unknown
  • 1987-10-13 PT PT85914A patent/PT85914B/pt not_active IP Right Cessation
  • 1987-10-13 CA CA000549084A patent/CA1325638C/en not_active Expired - Fee Related
  • 1987-10-13 SU SU874203489A patent/SU1588279A3/ru active
  • 1987-10-13 BE BE8701171A patent/BE1000617A4/fr not_active IP Right Cessation
  • 1987-10-13 US US07/107,050 patent/US5043440A/en not_active Expired - Fee Related
  • 1987-10-14 HU HU874642A patent/HU200325B/hu not_active IP Right Cessation
  • 1987-10-14 GB GB8724099A patent/GB2196340B/en not_active Expired - Fee Related
  • 1987-10-14 SE SE8704000A patent/SE8704000L/xx not_active Application Discontinuation
  • 1987-10-14 NL NL8702458A patent/NL8702458A/nl not_active Application Discontinuation
  • 1987-10-14 JP JP62259442A patent/JPS63112559A/ja active Pending
  • 1987-10-14 KR KR870011365A patent/KR890005048A/ko not_active Application Discontinuation

Patent Citations (5)

Non-Patent Citations (6)

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